tbuckley/cabot-search huggingface dataset:
PB1777: DEVELOPMENT OF NEXT GENERATION SEQUENCING PANELS FOR SCREENING FUSION GENES IN LEUKEMIA
Authors: S. Çiğdem, M. Arikan, E. Keskin
Journal: HemaSphere (2022)

Background: Diagnosis of hematologic malignancies is based on multidisciplinary approaches including cytological, cytogenetic, and molecular genetic analyzes. Advances in cancer genomics have enabled the identification of recurrent mutations with the apparent prognostic value for various cancers. To date, hundreds of fusion genes resulting from chromosomal rearrangements have been identified in acute leukemia. Testing such mutations in leukemias is essential for personalized treatments. Many methods used in conventional clinical diagnosis could not fully detect fusion genes. Aims: To overcome the limitations of existing techniques, targeted next generation sequencing approach was tested in this study. Methods: The libraries of the regions containing the junctions of the fusion genes, formed by multiplex PCR-based panels, was deep-sequenced using Illumina platform, thereafter the results were analyzed by bioinformatics approaches. Results: Using AmpliSeq (Illumina) fusion panel adapted for 20 KMT2A fusion transcripts and DNA fragments mimicking these fusion transcripts, 19 amplicons could be obtained with mPZR. With NGS procedures and bioinformatics analyses, significant results were obtained for 17 amplicons, while few junction reads that precisely describe the fusion event were obtained for the remaining 3. In titration studies, it was shown that the fusion panel can detect the template DNA fragments in trace amounts up to 1 pg. Image:Summary/Conclusion: These results show that the fusion panel can be used in clinical diagnosis for the fusion transcripts in its scope, after testing on clinical specimens.
P1555: IRON CHELATION THERAPY IN CONGENITAL HEMOLYTIC ANEMIAS: AN ITALIAN SINGLE CENTER STUDY
Authors: A. Bosi, B. Fattizzo, J. A. Giannotta, I. Papetti, W. Barcellini
Journal: HemaSphere (2022)

Background: Congenital hemolytic anemias (CHAs) can be associated with iron overload due to chronic hemolysis, ineffective erythropoiesis and, in some cases, red blood cell transfusions. Because of the rarity of these conditions, the appropriate management of iron chelation is poorly known and mainly based on thalassemia experience. Aims: To evaluate frequency, duration, efficacy and tolerability of iron chelation in patients with CHAs followed at our reference center. Methods: Clinical and laboratory data were retrospectively collected from patients who had documented history of iron chelation. Data were collected at time of diagnosis, at time of starting chelation and at variable times from treatment beginning. Follow-up data were censored at February 1st 2022. Results: 206 patients were retrospectively reviewed (151 with membrane defects, 31 with enzyme defects and 24 with congenital dyserythropoietic anemias – CDAs, Table 1). Twenty-six patients (13%) received iron chelation, mostly those with enzyme defects (35%) or CDAs (38%); at variance, only 4% of patients with membrane defects required chelation (p < 0.0001). Transfusion status showed that 31% of patients had history of transfusion-dependence (TD) (5 with Pyruvate kynase deficiency and 3 CDAs), 38% had received occasional transfusions and 31% had never received transfusions. Iron chelator was parenteral deferoxamine (DFA) or oral deferasirox (DFX), with a median daily dose of 573 mg for DFA and 584 mg for DFX. Median duration of treatment was 91 months with a wide range (3 – 372), including patients who received intermittent dosing (42%) and those on continuous chelation (58%). Concerning efficacy, median variation of serum ferritin from baseline was -51%, ranging from -94% to +6% (the latter in a patient who received a suboptimal dose). Overall, 64% of evaluable patients reduced ferritin below 500 ng/mL. Notably, a 33 year-old woman affected by CDA type II, with history of transfusion dependence since birth to age 9 y/o (time of splenectomy), developed cardiac iron overload with a cardiogenic shock. After a 4-year course of DFA, laboratory and imaging tests for iron overload markedly improved and her cardiac function recovered. Regarding toxicity, 5 out of 22 (23%) patients reported reversible renal (n = 2) and gastrointestinal adverse events (n = 2); one patient developed a non-fatal anaphylactic shock, leading to switch to a different chelator (from DFA to DFX). Image:Summary/Conclusion: Iron chelation was required in 13% of patients with CHAs, mostly among CDAs and enzyme defects, independently from transfusion requirements. It allowed a reduction of iron parameters in about 2/3 of cases with a good tolerability.
P1575: DEVELOPMENT OF A RISK PREDICTION MODEL OF SUBSEQUENT BLOOLDSTREAM INFECTION AFTER CARBAPENEM-RESISTANT ENTEROBACTERIACEASE ISOLATED FROM PERIANAL SWABS IN PATIENTS WITH HEMATOLOGICAL DISEASES
Authors: J. Liu, E. Jiang
Journal: HemaSphere (2022)

Background: Hematological patients are at higher risk of developing carbapenem-resistant Enterobacteriaceae (CRE) bloodstream infection (BSI) and associated with high mortality. Prediction model for a subsequent CRE BSI in hematological patients with CRE isolated from previous perianal swab samples can provide timely and useful target treatment strategies. Aims: To developing a quantified risk prediction model based on the risk factors of subsequent BSI in CRE carriers will help clinicians better identify specific individuals who would truly benefit from early, empiric CRE-targeted treatment. Methods: The data were extracted from patients with CRE isolated from perianal swab samples at the Hematopoietic Stem Cell Transplantation Center of Blood Diseases Hospital, Chinese Academy of Medical Sciences between July 2017 to October 2020 January. Patients who developed subsequent CRE BSI were compared with those who did not develop BSI. Univariate logistic analysis, multivariate logistic analysis and stepwise regression analysis were carried on a variety of clinical factors. Results: A total of 215 cases were included and 29 (13.4%) patients of them with CRE isolated from perianal swab samples developed CRE BSI subsequently. Multivariate analysis showed that C-reactive protein(CRP)﹥30mg/l(OR 10.613，95%CI 2.965~37.985，P=0.000）, perianal infection(OR 6.450, 95%CI 2.223~18.714, P=0.001), concomitant gastrointestinal symptoms (OR 4.175，95%CI 1.476~11.813，P=0.007），age﹥44 years (OR 3.415，95%CI 1.222~9.541，P=0.007）and neutrophil count﹤0.025×109/L (OR 4.583，95%CI 0.939~22.369，P=0.060）were risk factors for CRE BSI in patients with CRE isolated from perianal swab samples (P<0.01). They were included in the Logistic regression model to predict BSI. According to receiver operating characteristic (ROC) curve analysis, the cut-off value of the model was 0.921 (0.851-0.968，P<0.001). Image:Summary/Conclusion: Hematological patients with CRE isolated from perianal swab samples have a relatively low incidence of subsequent BSI but a relatively high risk of death. The risk prediction model based on CRP, perianal infection, concomitant gastrointestinal symptoms, age and valley absolute neutrophil may be used for predicting subsequent CRE BSI in patients with isolated from perianal swab samples and provide timely and effective treatment reference for this kind of patients.
PB1867: PURINE ANALOGS ON HAIRY CELL LEUKAEMIA TREATMENT
Authors: G. Gomes, I. Gonçalves, L. Rodrigues, F. Miranda, F. Mousinho, T. Mendes, A. Jorge, C. Claudino, P. Lupi, A. Reichert, C. Afonso
Journal: HemaSphere (2022)

Background: Hairy cell leukaemia (HCL) is a rare indolent neoplasm of small mature lymphoid cells. Most patients present with splenomegaly, cytopenias, characteristically monocytopenia, blood and marrow infiltration by neoplastic cells and infection susceptibility. Treatment with purine analogs is the first line standard of care with very good response rates. Cladribine (Cld) and Pentostatin (Pt) are described to induce similar response and relapse rates and safety profile. There continue to be though few therapeutic options after relapse. Aims: The aim of the study was to perform a comparative analysis of the treatment outcomes with Cld and Pt in a group of patients with HCL. Methods: A single-centre retrospective study of 22 patients was performed. Data was collected from clinical records. Results: Our study included 22 patients, 73% (16) male, with a median age at diagnosis of 62 years [33-80] and with 86% (19) with an Eastern Cooperative Oncology Group (ECOG) of 1 or less at diagnosis. All patients started treatment after diagnosis. 64% (14) received Pt as first line treatment and 36% (8) received Cld. Overall response rate was obtained in 86% (12) of patients treated with Pt - 5 with complete remission, 7 with partial remission and 2 with no response. An overall response was obtained in 100% of patients receiving Cld as first line treatment, with all patients achieving complete remission. Relapse was observed in 41% (9) of all patients. The relapse rate was of 41% (5) in patients treated with Pt and 50% (4) in patients treated with Cld. Median time until treatment after first line was of 38 months [9-232] – 37 months in the group treated with Pt and 39 months in the group treated with Cld. From the relapsed patients 7 received Cld as second line treatment, 1 received Pt and 1 Pt plus rituximab. Overall response was observed in all retreated patients. Summary/Conclusion: Our data confirms the well-recognised efficacy of purine analogs in the treatment of HCL in a real-world population of patients, presenting very good response rates both in first and subsequent treatment lines. Response rates were similar between Cld and Pt, as described in literature. However, Cld induced higher complete remission rates, although of similar duration, compared to Pt. Additional studies are needed for adequate stratification and identification of patients with higher risk of relapse in order to further improve response monitoring and treatment of these patients.
GP is suspended after retirement for failing to refer woman with symptoms of cancer
Authors: Clare Dyer
Journal: BMJ (2022)

Non-alcoholic fatty liver disease (NAFLD) is a globally prevalent health problem, associated in its more severe forms with increased liver-related and cardiovascular-related morbidity and mortality. We established a multidisciplinary metabolic hepatology clinic in 2014 and have analysed the clinical data to evaluate the effectiveness of this service. Patients with NAFLD (n=165) who had attended two or more appointments were included. Prespecified clinical data were collected prospectively at clinic appointments and analysed retrospectively. Interventions offered included lifestyle advice, signposting to weight loss services and pharmacological treatment of diabetes and cardiovascular risk factors. Median follow-up was 13 months (range: 2–34). 59% (n=97) of patients had type 2 diabetes mellitus (T2DM). 53% (n=87) underwent liver biopsy of whom 18% (n=16) had cirrhosis. Median alanine aminotransferase (ALT) reduced by 11 IU/L (p&lt;0.0001), median weight reduced by 3.3 kg (p=0.0005). There were significant reductions in HbA1c, total cholesterol and liver stiffness. Specifically, in patients with T2DM, HbA1c decreased by 4 mmol/mol (p=0.01) with significant reductions in ALT, weight and total cholesterol. Relative cardiovascular risk assessed by the QRISK3 score reduced in the whole cohort and in those with T2DM. Health economic modelling suggested the clinic intervention among those patients with poorly controlled T2DM was cost-effective. In conclusion, a multidisciplinary approach to the management of patients with NAFLD in this observational cohort study was associated with improvements in liver-related and cardio-metabolic related health parameters and with evidence of cost-effectiveness in patients with poorly controlled T2DM.
Shining a FLASHlight on Ultrahigh Dose-Rate Radiation and Possible Late Toxicity
Authors: Amit Maity, Constantinos Koumenis
Journal: Clinical Cancer Research (2022)

Summary A recent study reported results from a clinical trial in cats and from experiments in mini-pigs in which a single dose of radiotherapy was delivered at ultrahigh dose rates (FLASH). There was acceptable acute toxicity; however, some animals suffered severe late toxicity, raising caution in the design of future trials. See related article by Rohrer Bley et al., p. 3814
PB2162: INCREASED OXIDATIVE STRESS IN DIFFUSE LARGE B-CELL LYMPHOMA
Authors: D. Antic, D. Djikic, V. Otasevic, O. Mitrovic-Ajtic, V. Vukovic, T. Suboticki, V. Djurasinovic, K. Tomic, B. Mihaljevic, V. Cokic
Journal: HemaSphere (2022)

Background: Oxidative stress is caused by imbalance between excessive production of reactive oxygen species and decreased capabilities of antioxidant system, and it is recognized as a feature in cancerogenesis, as well in hematologic malignancies. Previous studies have shown increasing expression of oxidative stress markers and antioxidant enzymes in lymph nodes progressing to aggressive lymphomas. Aims: The aim of our study was to assess the clinical and prognostic significance of oxidative stress markers in patients with untreated diffuse large B-cell lymphoma (DLBCL). Methods: We analysed 64 patients diagnosed with DLBLC during 2018 and 2019, while 27 healthy volunteers (51.9% males) served as a control group. The plasma sample and laboratory analyses were obtained prior to initiation of specific hematologic treatment. After completion of the therapy, the patients were followed up for up to 4 years and for each of them progression free survival (PFS) and overall survival (OS) were calculated. Malondialdehyde (MDA) and protein carbonyl (PC) were used as markers of oxidative stress in plasma of patients and volunteers, while catalase is used as an antioxidant marker. Results: The mean patients’ age was 56.2 years (range, 20–87); 51.6% were males. Majority of patients were analysed before 1L therapy (n=61; 95,3%), and had following clinical stages: Ann Arbor stage I 23.4%, stage II 37.5%, stage III 15.6% and stage IV 23.4%. Majority of the patients had satisfactory performance status (73.5% had ECOG PS ≥1), bulky tumorous mass was present in 34.4% of patients, whereas 70.3% had extranodal localisation of lymphoma. MDA (6.66±2.7 nmol/ml) was significantly increased (p<0.001, 2.6-fold), while PC (4.29±2.7 nmol/mg) was also significantly increased (p=0.0027, 5-fold) in patients with DLBCL compared to healthy volunteers. In opposite, antioxidant catalase (0.194±0.06 IU/ml) was significantly reduced (p=0.0034, 1.9-fold) in patients with DLBCL. MDA was in significant (p<0.05) negative correlation with hemoglobin (r2=0.586) and LDH (r2=0.59) levels before chemotherapy. MDA was in significant (p<0.01) positive correlation with the age (r2=0.769) of patients with DLBCL at diagnosis. Moreover, MDA was in significant positive correlation with overall survival (p<0.01, r2=0.736) and progression-free survival (p<0.01, r2=0.736) of patients with DLBCL. PC was in negative correlation with the clinical stage (r2=0.103, p=0.146) and therapy response (r2=0.136, p=0.091) of DLBCL but did not reach significance. Summary/Conclusion: The elevated oxidative markers and reduced antioxidant support oxidative stress in patients with DLBCL, while MDA can be a prognostic marker of overall survival.
Haploidentical vs matched sibling donor transplant for paroxysmal nocturnal haemoglobinuria: A multicenter study
Authors: Limin Liu, Shunqing Wang, Erlie Jiang, Yanming Zhang, Jianyong Li, Yuewen Fu, Meiqing Lei, Kailin Xu, Mingzhen Yang, Yinghao Lu, Miao Miao, Depei Wu
Journal: Blood Cancer Journal (2022)
PB1946: ACQUIRED AMEGAKARYOCYTIC THROMBOCYTOPENA (AAMT), A SINGLE CENTER EXPERIENCE
Authors: S. Mohamed, S. Kohla, K. Ahmed, A. Amer, K. Obeidat, D. Soliman, F. Ibrahim
Journal: HemaSphere (2022)

Background: Acquired Amegakaryocytic Thrombocytopenia (AAMT) is a very rare hematological condition. There are few cases reported in the literature. It is characterized by severe thrombocytopenia with complete absence or severe reduction of megakaryocytes in the bone marrow, with otherwise normal hematopoiesis. The underlying mechanism for AAMT is not fully understood but is suggested to be related to anti-thrombopoietin (TPO) antibodies. The diagnosis of AAMT can be challenging for both clinicians and pathologists. On many occasions, it goes undiagnosed or misdiagnosed as Immune thrombocytopenic purpura (ITP). Aims: Describe patients (pts) or cases of AAMT diagnosed in our national center for cancer care and research (NCCCR) in Qatar. Methods: We retrospectively collected pts aged ≥ 18 years (yrs.) with AAMT based on bone marrow finding who had been diagnosed and/or treated between January 2011 and December 2021 at the (NCCCR) in Qatar. Results: Seven cases were identified; the median age was 43 years (25-55). Four patients were males and all of the patients were from Asian ethnicity. Complete blood count (CBC) showed HB with median of 9.2 gm/dl (6.6-11.8), white blood cells of 6.8 x10^3/ul (2.1- 9) and platelets 13 x10^9/L (5-20). Bone marrow biopsies showed suppressed or absence of megakaryocytic components in all patient with variable degrees of marrow cellularity. potential underlying etiologies identified in the cases were autoimmune disease, HBV, B12 deficiency and solid malignancy. Three patients progressed to frank aplastic anemia. Steroids plus intravenous Immunoglobulin (IVIGg) were the backbone of treatment of all patients since they were diagnosed as ITP first before bone marrow sampling. The addition of the thrombopoietin receptor agonist eltrombopag and immunosuppressant Cyclosporine improved the platelets’ response in five patients. Transplant was considered for patients who developed aplastic anemia however, not done due to improvement in counts or due to patients’ social reasons Image:Summary/Conclusion: In summary, AAMT is rare disease characterized by thrombocytopenia resulting from a marked decrease in bone marrow megakaryocytes. It’s very important to consider it in some cases of ITP as an alternative diagnosis specially in atypical cases or cases resistant to treatment. eltrombopag and Cyclosporine improved patients’ blood counts. There are no guidelines currently for the management of this rare condition
P1271: ELUCIDATING TUMOR SUPPRESSOR FUNCTIONS OF TET2 IN B CELL LYMPHOMAS
Authors: N. Kinz, S. Spoeck, M. Leone, M. Lohmueller, A. Villunger, V. Labi
Journal: HemaSphere (2022)

Background: Remodeling of the epigenetic landscape via DNA cytosine methylation directs cell lineage specification, establishing and maintaining gene expression programs that uniquely define given cell types. During tumorigenesis the epigenome becomes corrupted, impairing lineage-specific gene expression programs. TET2, an enzyme that contributes to the erasure of cytosine methylation via oxidation of the 5’ methyl group, is among the most frequent somatically mutated genes in human hematological tumors, commonly identified as loss-of-function versions. In mouse models, TET2 loss on its own is only weakly tumorigenic, but rather facilitates leukemic transformation driven by prototypic oncogenes such as AML-ETO or FLT3ITD. However, TET2 LOF is not limited to leukemias. In B cell malignancies, TET2 is found mutated in a fraction of diffuse large B cell lymphomas (DLBCL), which display a distinct gene expression profile. Aims: Having established a role for TET2 loss-of-function in enhancing MYC-driven lymphomas, our overall aim is to understand how TET2 loss conspires with MYC to overcome the barriers that maintain cell identity and function. Methods: Using pre-clinical mouse models and in vitro culture systems, we establish that TET2 loss boosts the formation of B cell lymphomas driven by the MYC oncoprotein. Results: Thus, (1) TET2 deficiency specifically in B cells facilitates MYC-mediated transformation in a dose dependent manner, and (2) TET2 deficiency early on in hematopoietic stem and progenitor cells enhances the transformative potential later on in antigen-activated B cells. Our data suggest that TET2 may exert tumor suppressor functions via controlling the expression of DNA repair genes, or via direct functions of oxidized cytosine species. In addition, TET2-deficient lymphomas select for high expression of the pro-survival BCL2 family protein BCLXL, potentially providing protection from MYC-driven apoptosis. Summary/Conclusion: Altogether, our data concerning the impact of TET2 loss-of-function on DNA repair and apoptosis mechanisms creates understanding of how TET2 deficiency nudges transformation, and reveals testable therapeutic vulnerabilities.
FDA Approval Summary: Belantamab Mafodotin for Patients with Relapsed or Refractory Multiple Myeloma
Authors: Andrea C. Baines, Rachel Ershler, Bindu Kanapuru, Qing Xu, Guoxiang Shen, Liang Li, Lian Ma, Olanrewaju O. Okusanya, Natalie E. Simpson, Wanda Nguyen, Marc R. Theoret, Richard Pazdur, Nicole J. Gormley
Journal: Clinical Cancer Research (2022)

Abstract On August 5, 2020, the FDA granted accelerated approval to belantamab mafodotin-blmf (BLENREP; GlaxoSmithKline) for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. Substantial evidence of effectiveness was obtained from the phase II, multicenter DREAMM-2 trial. Patients received belantamab mafodotin 2.5 or 3.4 mg/kg intravenously once every 3 weeks until disease progression or unacceptable toxicity. The trial demonstrated an overall response rate of 31% in the 2.5 mg/kg cohort and 34% in the 3.4 mg/kg cohort. Keratopathy was the most frequent adverse event, occurring in 71% and 77% of patients, respectively. Other ocular toxicities included changes in visual acuity, blurred vision, and dry eye. The U.S. prescribing information for belantamab mafodotin includes a boxed warning for ocular toxicity, and belantamab mafodotin is available only through a restricted program under a Risk Evaluation and Mitigation Strategy. This article summarizes the data and the FDA review process supporting accelerated approval of belantamab mafodotin 2.5 mg/kg intravenously once every 3 weeks. This approval may be contingent upon verification and description of clinical benefit in confirmatory trial(s).
Abstract SY41-02: Epigenetic influence of our (fatty) diet on metastatic-initiating cells: Role of intra-tumor Schwann cells
Authors: Salvador Aznar-Benitah
Journal: Cancer Research (2022)

Abstract We have recently identified the cells uniquely responsible for the formation of metastasis in different types of human tumors. These cells have intriguing characteristics: i) they form primary lesions as efficiently as their tumor-initiating counterparts, but are exclusive in their ability to generate metastases; ii) they express the fatty acid translocase CD36, and are characterized by a unique lipid metabolic signature; iii) they are exquisitely sensitive to the levels of fat in circulation, and consequently, they relate the predisposition of metastasis directly to the content of dietary fat; iv) they are highly sensitive to CD36 inhibition, which almost completely abolishes their metastatic potential in preclinical models. In my talk, I will present our latest data on the molecular characterization of metastatic-initiating cells. I will place special emphasis showing how specific dietary lipids exert a striking long-term epigenetic effect over metastatic-initiating cells related to activation of intra-tumor Schwann cells, putting forward a novel concept of ¨metastatic epigenetic memory¨ elicited by our diet. Citation Format: Salvador Aznar-Benitah. Epigenetic influence of our (fatty) diet on metastatic-initiating cells: Role of intra-tumor Schwann cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr SY41-02.